Nephronectin, also called POEM (preosteoblast EGF repeat protein with MAM domain) is a 70 - 90 kDa extracellular matrix protein that is a ligand for integrin alpha8beta1. Nephronectin is most highly expressed in developing endocrine organs such as parathyroid, thyroid, hypophysis and pineal organ, and around developing bone, teeth, and muscle. Pre-osteoblast cells produce nephronectin, but downregulate it as they differentiate. It is also expressed in the Wolffian duct and ureteric bud basement membranes in the developing kidney, where it is colocalizes, and forms an in vivo complex with integrin alpha8beta1. Since deletion of integrin alpha8beta1 results in renal agenesis, nephronectin has been proposed to be a critical integrin alpha8beta1 ligand during nephrogenesis.
The 561 aa mouse nephronectin (isoform B) contains a 19 amino acid (aa) signal sequence, a matrilin-type vWA domain, two calcium-binding EGF-like domains, a potential N-linked glycosylation site, a pro/ser/thr-rich mucin-like region, an RGD integrin binding motif, and a MAM domain. These features are often present in matrix proteins that, like nephronectin, mediate cell adhesion and spreading. Isoform A includes a 17 aa insertion between aa # 58 and 59 that is missing in Nephronectin isoform B. Mouse nephronectin shows 88%, 92%, 85% and 77% aa identity with human, rat, cow and opossum nephronectin, respectively.